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Q8NAU1 (FNDC5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fibronectin type III domain-containing protein 5
Alternative name(s):
Fibronectin type III repeat-containing protein 2

Cleaved into the following chain:

  1. Irisin
Gene names
Name:FNDC5
Synonyms:FRCP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length212 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Irisin: Contrary to mouse, may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue (Ref.8). Ref.8

Subcellular location

Cell membrane; Single-pass type I membrane protein. Peroxisome membrane; Single-pass type I membrane protein By similarity. Note: Imported in peroxisomes through the PEX5 receptor pathway By similarity. Ref.7

Irisin: Secreted. Note: Detected in the blood of individuals subjected to endurance exercise (Ref.7). Ref.7

Tissue specificity

Widely expressed, with highest levels in heart. Very low expression, if any, in colon, pancreas and spleen. Ref.8

Induction

Has been shown to be up-regulated some twofold by muscular exercise at the mRNA and protein level; this effect has been suggested to be mediated by PPARGC1A (Ref.7). However, up-regulation upon exercise could not be reproduced, at least not at the mRNA level (Ref.8). Ref.7 Ref.8

Post-translational modification

The extracellular domain is cleaved and released from the cell membrane.

N-Glycosylated By similarity.

Sequence similarities

Contains 1 fibronectin type-III domain.

Caution

It is uncertain whether Met-1 or Met-76 is the initiator. Transcript evidence available at present time points at Met-76. In this short version of the protein, the signal peptide cannot be predicted and the irisin peptide is severely truncated. The first initiation codon corresponds to a non-AUG site, an N-terminal ATA codon. This initiation codon has been annotated as it is in good Kozak context and it is conserved in other primates, including gibbon, chimpanzee and gorilla. Although the existence of such a form has not been demonstrated in human, western blot analysis following endurance exercise shows the presence of an irisin peptide of similar size in human and mouse plasma (Ref.7), suggesting the existence of full length irisin in human, at least in some tissues. However, expression from Met-1 may be less efficient than that from Met-76 (Ref.8).

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8NAU1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8NAU1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     180-181: KD → EA
     182-212: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8NAU1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.
     212-212: I → VRARPGPGWATLCLMLW
Note: No experimental confirmation available.
Isoform 4 (identifier: Q8NAU1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Chain32 – 212181Fibronectin type III domain-containing protein 5
PRO_0000328971
Chain32 – 143112Irisin
PRO_0000415857

Regions

Topological domain32 – 152121Extracellular Potential
Transmembrane153 – 17321Helical; Potential
Topological domain174 – 21239Cytoplasmic Potential
Domain36 – 12792Fibronectin type-III
Motif210 – 2123Microbody targeting signal Potential

Amino acid modifications

Glycosylation391N-linked (GlcNAc...) Potential
Glycosylation841N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 7575Missing in isoform 3 and isoform 4.
VSP_032860
Alternative sequence180 – 1812KD → EA in isoform 2.
VSP_032861
Alternative sequence182 – 21231Missing in isoform 2.
VSP_032862
Alternative sequence2121I → VRARPGPGWATLCLMLW in isoform 3.
VSP_032863

Secondary structure

................ 212
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 5, 2012. Version 3.
Checksum: C4A066452A05A134

FASTA21223,659
        10         20         30         40         50         60 
MHPGSPSAWP PRARAALRLW LGCVCFALVQ ADSPSAPVNV TVRHLKANSA VVSWDVLEDE 

        70         80         90        100        110        120 
VVIGFAISQQ KKDVRMLRFI QEVNTTTRSC ALWDLEEDTE YIVHVQAISI QGQSPASEPV 

       130        140        150        160        170        180 
LFKTPREAEK MASKNKDEVT MKEMGRNQQL RTGEVLIIVV VLFMWAGVIA LFCRQYDIIK 

       190        200        210 
DNEPNNNKEK TKSASETSTP EHQGGGLLRS KI 

« Hide

Isoform 2 [UniParc].

Checksum: 36BEE521AFABE5A6
Show »

FASTA18120,281
Isoform 3 [UniParc].

Checksum: 4DA2ABEAC5B4D934
Show »

FASTA15317,323
Isoform 4 [UniParc].

Checksum: 1045BF9CE29A41E4
Show »

FASTA13715,527

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Brain.
[5]The Cancer Genome Anatomy Project (CGAP) at the National Cancer Institute
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-133 (ISOFORM 1).
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-212 (ISOFORM 2).
Tissue: Fetal liver.
[7]"A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis."
Bostrom P., Wu J., Jedrychowski M.P., Korde A., Ye L., Lo J.C., Rasbach K.A., Bostrom E.A., Choi J.H., Long J.Z., Kajimura S., Zingaretti M.C., Vind B.F., Tu H., Cinti S., Hojlund K., Gygi S.P., Spiegelman B.M.
Nature 481:463-468(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, SUBCELLULAR LOCATION.
[8]"Evidence against a Beneficial Effect of Irisin in Humans."
Raschke S., Elsen M., Gassenhuber H., Sommerfeld M., Schwahn U., Brockmann B., Jung R., Wisloff U., Tjonna A.E., Raastad T., Hallen J., Norheim F., Drevon C.A., Romacho T., Eckardt K., Eckel J.
PLoS ONE 8:E73680-E73680(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK092102 mRNA. Translation: BAC03806.1.
AC114493 Genomic DNA. No translation available.
CH471059 Genomic DNA. Translation: EAX07499.1.
CH471059 Genomic DNA. Translation: EAX07502.1.
CH471059 Genomic DNA. Translation: EAX07500.1.
BC062297 mRNA. Translation: AAH62297.1.
BX537781 mRNA. Translation: CAD97840.1.
BF221649 mRNA. No translation available.
CCDSCCDS369.2. [Q8NAU1-1]
CCDS65483.1. [Q8NAU1-3]
RefSeqNP_001165411.2. NM_001171940.1. [Q8NAU1-2]
NP_001165412.1. NM_001171941.2. [Q8NAU1-3]
NP_715637.2. NM_153756.2. [Q8NAU1-1]
UniGeneHs.524234.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4LSDX-ray2.28A/B/C/D/E/F/G/H33-130[»]
ProteinModelPortalQ8NAU1.
SMRQ8NAU1. Positions 33-130.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000362570.

PTM databases

PhosphoSiteQ8NAU1.

Polymorphism databases

DMDM403314395.

Proteomic databases

PaxDbQ8NAU1.
PRIDEQ8NAU1.

Protocols and materials databases

DNASU252995.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000496770; ENSP00000476320; ENSG00000160097. [Q8NAU1-3]
ENST00000609187; ENSP00000476668; ENSG00000160097. [Q8NAU1-4]
GeneID252995.
KEGGhsa:252995.
UCSCuc001bwf.2. human. [Q8NAU1-1]
uc001bwg.3. human. [Q8NAU1-3]

Organism-specific databases

CTD252995.
GeneCardsGC01M033327.
HGNCHGNC:20240. FNDC5.
HPAHPA051290.
MIM611906. gene.
neXtProtNX_Q8NAU1.
PharmGKBPA134924607.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG87775.
HOGENOMHOG000082536.
HOVERGENHBG067308.
InParanoidQ8NAU1.
OMAPDENGME.
OrthoDBEOG7S2206.
TreeFamTF325415.

Gene expression databases

BgeeQ8NAU1.
CleanExHS_FNDC5.
GenevestigatorQ8NAU1.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR003961. Fibronectin_type3.
IPR013783. Ig-like_fold.
[Graphical view]
PfamPF00041. fn3. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 1 hit.
PROSITEPS50853. FN3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi252995.
NextBio92038.
PROQ8NAU1.
SOURCESearch...

Entry information

Entry nameFNDC5_HUMAN
AccessionPrimary (citable) accession number: Q8NAU1
Secondary accession number(s): A6NMC9 expand/collapse secondary AC list , D3DPQ6, Q6P6D9, Q7Z676
Entry history
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: September 5, 2012
Last modified: July 9, 2014
This is version 104 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM